Once the probes were fully advanced into the brain, we observed a decline in the compression force over time.

However, the compression force never decreased to zero.

This may indicate that chronically implanted probes experience a constant compression force when inserted in the brain, which may push the probe out of the brain over time if there is nothing to keep it in a fixed position.

Yet ... the Utah probe seems fine, up to many months in humans.

This may be a drawback for flexible probes [24], [25]. The approach to reduce tissue damage by reducing micromotion by not tethering the probe to the skull can also have this disadvantage [26]. Furthermore, the upward movement may lead to the inability of the contacts to record signals from the same neurons over long periods of time.

We did not observe a difference in initial insertion force, amount of dimpling, or the rest force after a 3-min rest period, but the force at the end of the insertion was significantly higher when inserting at 100 μm/s compared to 10 μm/s.

No significant difference in histological response observed between the two speeds.

(Interesting): eight identical electrode arrays implanted into the same region of different animals have shown that half the arrays continue to record neural signals for >14 weeks while in the other half of the arrays, single-unit yield rapidly degraded and ultimately failed over the same timescale.

In another study, aimed at uncovering the time course of insertion-related bleeding and coagulation, electrodes were implanted into the cortex of rats at varying time intervals (−120, −90, −60, −30, −15, and 0 min) using a micromanipulator and linear motor with an insertion speed of 2 mm/s.40 The results showed dramatic variability in BBB leakage that washed out any trend (Figure 3), suggesting that a separate underlying cause was responsible for the large inter- and intra-animal variability.

One of the goals/needs of the lab is to be able to stimluate and record nervous tissue at the same time. We do not have immediate access to optogenetic methods, but what about lower frequency EM stimulation? The idea: if you put the stimulation frequency outside the recording system bandwidth, there is no need to switch, and indeed no reason you can't stimulate and record at the same time.

Hence, I very briefly checked for the effects of RF stimulation on nervous tissue.

shows that neurons are activated by pulsed RF, albeit through c-Fos staining. Electrodes were much larger in this study.

Also see PMID-15618777[3]associated editorial which calls for more extensive clinical, controlled testing. The editorial gives some very interesting personal details - scientists from the former Soviet bloc!

PMID-16310722[4]Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons.

used 20ms pulses of 500kHz.

Small diameter fibers are differentially activated.

Pulsed RF induces activating transcription factor 3 (ATF3), which has been used as an indicator of cellular stress in a variety of tissues.

However, there were no particular signs of axonal damage; hence the clinically effective analgesia may be reflective of a decrease in cell activity, synaptic release (or general cell health?)

Implies that RF may be dangerous below levels that cause tissue heating.

The important result is that materials with low protein-binding (e.g. alginate) have fewer bound microglia, hence better biocompatibility. It also seems to help if the material is highly hydrophilic.

Yes alginate is made from algae.

Used Michigan probes for implantation.

ED1 = pan-macrophage marker.

(quote:) Quantification of cells on the surface indicated that the number of adherent microglia appeared higher on the smooth side of the electrode compared to the grooved, recording site side (Fig. 2B), and declined with time. However, at no point were electrodes completely free of attached and activated microglial cells nor did these cells disappear from the interfacial zone along the electrode tract.

We have developed an ex vivo preparation to capture real-time images of tissue deformation during device insertion using thick tissue slices from rat brains prepared with fluorescently labeled vasculature.

Direct damage to the vasculature included severing, rupturing and dragging, and was often observed several hundred micrometers from the insertion site. (yikes!)

Important point: ED1 up-regulation and neuronal loss were not observed in microelectrode stab controls, indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response.

Only tested response 2 and 4 weeks after implantation. Makes sense for stab wound, but didn't the want to see a longer term response? Or do their electrodes just not last that long?

What did they coat the silicon probes in?

Used silastic to shock-mount their floating electrodes, but this apparently made no difference compared to conventional dental cement and bone screw mounting.

Suggest that chronic inflammatory response may be related to the absorption of fibrogen and complement to the surface of the device (device should not be porous?), the subsequent release of pro-inflammatory and cytotoxic cytokines by activated microphages, and the persistence of activated macrophages around materials which cannot be broken down.

Well then, how do you make the electrodes biochemically / biologically 'invisible'?

Persistently activated microglia are found around insoluble plaques in AD (plaques that cannot be / are not removed from the brain via proteolysis. Microglia form 'glitter cells' when they engulf undigestible stubstances). This has been termed 'frustrated phagocytosis', which results in increased secretion of proinflamatory cytokines that directly or indirectly cause neuronal death.

Significant reductions in neurofiliament reactivity was seen up to 230um from the microelectrode interface; this was not seen for stab wounds. Maximum recording distance is about 130um; 100um more reasonable in normal conditions.

Accumulating evidence from postmortem analysis of patients implanted with DBS electrodes reveals that chronic neuroinflamation is part of the response to such (duller, larger) implants as well. They have seen cell loss up to 1mm fromt the electrode surface here.